Lymphoma, B-CellPhase 1NCT01055496
Study Evaluating Chemotherapy in Combination With Inotuzumab Ozogamicin In Subjects With Non-Hodgkin's Lymphoma
A Phase 1 study testing inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone and inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone in people with Lymphoma, B-Cell, run by Pfizer at 28 sites in 9 countries.
Trial summary
This is a phase 1 trial designed to evaluate safety and tolerability of chemotherapy in combination with inotuzumab ozogamicin, an investigational product, in adults with CD22-positive non-Hodgkin's lymphoma. The trial will involve two arms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, B-Cell
- What is being tested?
- inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone and inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 28 sitesin 9 countries
- Study dates
- Mar 2010to Mar 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Dose escalation cohorts: subjects with diagnosis of CD22-positive Non-Hodgkin's Lymphoma (NHL) who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy.
- Expanded maximum tolerated dose (MTD) confirmation and preliminary efficacy cohorts: subjects with diagnosis of CD22-positive NHL who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy or newly diagnosed subjects who are not candidates for anthracycline-based therapy.
- At least 1 measurable disease lesion that is > 1 cm in the longest transverse diameter, with a product of the diameters > 2.25 cm2 by CT or magnetic resonance imaging (MRI).
Who cannot join
- Candidate for potentially curative therapy such as stem cell transplantation.
- Prior allogeneic hematopoietic stem cell transplantation (HSCT).
- Prior autologous transplantation, radioimmunotherapy, or other anti CD22 immunotherapy <= 6 months before the first dose of investigational product.
- More than 3 previous combination chemotherapy (2 or more cytotoxics) anticancer regimens.
Trial locations and contacts
28 sites in 9 countries.
28 sites in 9 countries
United States10 sites
Northwest Medical Specialties, PLLC
Federal Way, Washington, 98003
Davis Cancer Pavillion and Shands Medical Plaza
Gainesville, Florida, 32608
Shands Cancer Hospital At The University Of Florida
Gainesville, Florida, 32608
Shands Hospital at the University of Florida
Gainesville, Florida, 32610
Northwest Medical Specialties, PLLC
Gig Harbor, Washington, 98332
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4009
Northwest Medical Specialties, PLLC
Lakewood, Washington, 98499
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
Rainier Physicians, PC
Puyallup, Washington, 98373
Northwest Medical Specialties PLLC
Tacoma, Washington, 98405
United Kingdom4 sites
Nuffield Hospital
Eastleigh, Hants, SO53 2DW
Guy's and St Thomas' NHS Foundation Trust
London, SE1 9RT
Spire Southampton Hospital
Southampton, Hants, SO16 6UY
Cancer Sciences Division, Somers Cancer Research Building
Southampton, Hants, SO16 6YD
Canada3 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Queen Elizabeth Health Sciences Centre
Halifax, Nova Scotia, B3H 2Y9
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
France3 sites
Hopital Saint-Louis -Universite Paris VII
Paris, 75010
Hospital Saint-Louis - Service d'Hemato-Oncologie
Paris, 75475
Centre Hospitalier Lyon Sud - Service d'Hematologie
Pierre-Bénite, 69495
Japan3 sites
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
Cancer Institute Hospital, Japanese Foundation For Cancer Research
Koto-Ku, Tokyo, 135-8550
Nagoya Daini Red Cross Hospital
Nagoya, Aichi-ken, 466-8650
About this study
Official title: AN OPEN-LABEL, PHASE 1 STUDY OF R-CVP OR R-GDP IN COMBINATION WITH INOTUZUMAB OZOGAMICIN IN SUBJECTS WITH CD22-POSTIVE NON-HODGKIN'S LYMPHOMA
This is a phase 1 trial designed to evaluate safety and tolerability of chemotherapy in combination with inotuzumab ozogamicin, an investigational product, in adults with CD22-positive non-Hodgkin's lymphoma. The trial will involve two arms. In one arm, subjects will receive chemotherapy regimen R-CVP (rituximab, cyclophosphamide, vincristine and prednisone). In the other arm, subjects will receive R-GDP (rituximab, gemcitabine, cisplatinum and dexamethasone). Subjects in both arms will also receive inotuzumab ozogamicin.
- Conditions
- Lymphoma, B-Cell
- Being tested
- inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone, inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone
- Keywords
- Non-Hodgkin's lymphoma
- Medical subject headings
- Lymphoma, B-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisoneDrug
Also called CMC-544
Day 1:
Rituximab at 375 mg/m2 Cyclophosphamide at 375 mg/m2 (cohort 1), 550mg/m2 (cohort 2), 750 mg/m2 (cohort 3, 4) Vincristine at 1.4 mg/m2 (max 2 mg)
Day 2 Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2, 3), 1.3 mg/m2 (cohort 4)
Days 1-5:
Prednisone at 40 mg/m2
Each cycle is 3 weeks, with a maximum of 6 cycles total.
inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasoneDrug
Also called CMC-544
Day 1:
Rituximab at 375 mg/m2 Gemcitabine at 500 mg/m2 (cohort 1, 2b, 3b), 1000mg/m2 (cohort 2a, 3a, 4, 5) Cisplatin at 37.5 mg/m2 (cohort 1, 2a), 50mg/m2 (cohort 2b, 3a), 75mg/m2 (cohort 3b, 4, 5)
Day 2:
Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2a, 2b, 3a, 3b, 4), 1.3mg/m2 (cohort 5)
Days 1-4:
Dexamethasone at 40 mg
Each cycle is 3 weeks, with a maximum of 6 cycles total.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (R-CVP) | Experimental | Subjects in arm 1 will be enrolled in dose escalation cohorts that will initially evaluate an escalating dose of cyclophosphamide in combination with set doses of inotuzumab ozogamicin, vincristine, prednisone, and rituximab. Receives: Drug: inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone |
| Arm 2 (R-GDP) | Experimental | Subjects in arm 2 will be enrolled in dose escalation cohorts that will initially evaluate escalating doses of gemcitabine and/or cisplatinum in combination with set doses of inotuzumab ozogamicin, dexamethasone, and rituximab. Receives: Drug: inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants Reporting Dose Limiting Toxicity (DLT) Adverse Events (AEs) for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 1
DLT was defined as: febrile neutropenia, Grade (Gr) 4 neutropenia ≥7 days, Gr 4 thrombocytopenia ≥7 days, Gr 3/4 thrombocytopenia associated with bleeding requiring a transfusion, Gr 3/4 non-hematologic toxicity (except alopecia) ≥7 days or treatment-related and clinically significant irrespective of duration, ≥Gr 3 QTc prolongation, Gr 4 alanine or aspartate aminotransferase, Gr 2 hyperbilirubinemia (greater than (>)1.5 x upper normal limit) >7 days, delayed recovery from a treatment-related toxicity that prevented re-dosing by >7 days, or Granulocyte-colony stimulating factor treatment during the first cycle.
Measured: From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.
Participants Reporting DLT AEs for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 2
DLT was defined as: febrile neutropenia, Grade (Gr) 4 neutropenia ≥7 days, Gr 4 thrombocytopenia ≥7 days, Gr 3/4 thrombocytopenia associated with bleeding requiring a transfusion, Gr 3/4 non-hematologic toxicity (except alopecia) ≥7 days or treatment-related and clinically significant irrespective of duration, ≥Gr 3 QTc prolongation, Gr 4 alanine or aspartate aminotransferase, Gr 2 hyperbilirubinemia (greater than (>)1.5 x upper normal limit) >7 days, delayed recovery from a treatment-related toxicity that prevented re-dosing by >7 days, or Granulocyte-colony stimulating factor treatment during the first cycle.
Measured: From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.
Percentage of Participants With Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) According to International Response Criteria for NHLs in the MTD and EE Cohorts
OR was evaluated according to the International Response Criteria for NHLs. CR was defined as complete disappearance of all lesions and disease-related symptoms; all nodes must have decreased to normal (less than or equal to [≤]1.5 centimeters [cm] in their greatest transverse diameter (GTD) for nodes >1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy. PR was defined as >50% decrease in the sum of the product diameters (SPD) of up to 6 index lesions. No increase in size of other nodes, liver or spleen. Splenic and hepatic nodules must have regressed by ≥50% in the SPD or GTD (for single nodules). With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.
Measured: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks.
Percentage of Participants With a Treatment Emergent AE
An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event may not necessarily have had a causal relationship with the treatment or usage. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were defined as those occurring on or after the first study drug dose day through and including 56 days post last dose of study drug. The severity of all AEs was graded by the investigator using the National Cancer Institute Common Terminology Criteria for AE Version 3.0 (NCI CTCAE v3.0).
Measured: SAEs were assessed from informed consent through and including the end of treatment visit (at least 28 calendar days after last study drug administration). Non-SAEs were recorded from time of the first dose of study drug through last participant visit.
Percentage of Participants With Any Grade 3/4 Chemistry Abnormality During Therapy
The following parameters were analyzed for blood chemistry: blood urea nitrogen (or urea), creatinine, glucose, calcium, sodium, potassium, phosphorus, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, total bilirubin (and direct bilirubin, if total bilirubin was elevated), alkaline phosphatase, uric acid (or urate), albumin and total protein. Laboratory test results were graded using the NCI CTCAE v3.0 where CTCAE Grade 3 equals "severe" and CTCAE Grade 4 equals "life threatening or disabling."
Measured: Within 3 days prior to the start of each cycle, on Day 8 of each cycle, on Day 15 of Cycles 1, 2, and 3, and the end-of-treatment visit. Each Cycle is 21 Days.
Percentage of Participants With Any Grade 3/4 Hematology Abnormality During Therapy
The following parameters were analyzed for hematology: lymphocytes, basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, monocytes, neutrophils, platelets, prothrombin international normalized ratio, prothrombin time, fibrinogen, and activated partial thromboplastin time. Laboratory test results were graded using the NCI CTCAE v3.0 where CTCAE Grade 3 equals "severe" and CTCAE Grade 4 equals "life threatening or disabling."
Measured: Within 3 days prior to the start of each cycle, Day 8 of each cycle, Day 15 of Cycles 1, 2, and 3, and the end-of-treatment visit. Each Cycle is 21 Days.
Secondary outcomes (10)
Percentage of Participants With a Best OR of CR or PR According to International Response Criteria for NHLs in the DE Cohorts
OR was evaluated according to the International Response Criteria for NHLs. CR was defined as complete disappearance of all lesions and disease-related symptoms; all nodes must have decreased to normal (≤1.5 cm in their GTD for nodes >1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy. PR was defined as >50% decrease in the SPD of up to 6 index lesions. No increase in size of other nodes, liver or spleen. Splenic and hepatic nodules must have regressed by ≥50% in the SPD or GTD (for single nodules). With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.
Measured: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks.
Kaplan-Meier Estimate of the Progression-Free Survival (PFS) in the DE Cohorts
PFS was defined as time from date of first dose to the earlier date of progression (including symptomatic deterioration), date of death from any cause, or initiation of new anticancer therapy for the lymphoma. Participants without an event were censored at the date of the last valid tumour assessment. A valid tumour assessment visit was defined as the tumour assessment visit with overall response of CR, PR, stable disease (SD), or disease progression (PD), but not 'Not Done' or 'Unknown'. Participants without a post-baseline tumour assessment and without a PFS event were censored on the date of first dose.
Measured: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the DE Cohorts
Measure includes death from any cause, PD (including symptomatic deterioration) during and after treatment or initiation of new anticancer therapy for the lymphoma. PD was defined as symptomatic deterioration and according to the International Response Criteria for NHL: 1) appearance of any new lesion >1.5 cm in any axis during or at EOT, even if other lesions are decreasing, 2) at least a 50% increase from nadir in the SPD of any previously involved or single involved nodes, or the size of other lesions (splenic or hepatic). Lymph nodes with a short axis diameter of <1.0 cm must increase by ≥50% and to a size of 1.5x1.5 cm or >1.5 cm in the long axis, 3) 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis. PD was defined as clinical PD, new non-nodal lesions or new nodal lesion ≥1.5 cm in GTD, progression of existing non-index lesions or bone marrow that was negative and now positive.
Measured: 6, 12 and 24 months
Kaplan-Meier Estimate of the PFS in the MTD Confirmation/EE Cohorts
PFS was defined as time from date of first dose to the earlier date of progression (including symptomatic deterioration), date of death from any cause, or initiation of new anticancer therapy for the lymphoma. Participants without an event were censored at the date of the last valid tumour assessment. A valid tumour assessment visit was defined as the tumour assessment visit with OR of CR, PR, SD, or PD, but not 'Not Done' or 'Unknown'. Participants without a post-baseline tumour assessment and without a PFS event were censored on the date of first dose.
Measured: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts.
Measure includes death from any cause, PD (including symptomatic deterioration) during and after treatment or initiation of new anticancer therapy for the lymphoma. PD was defined as symptomatic deterioration and according to the International Response Criteria for NHL: 1) appearance of any new lesion >1.5 cm in any axis during or at EOT, even if other lesions are decreasing, 2) at least a 50% increase from nadir in the SPD of any previously involved or single involved nodes, or the size of other lesions (splenic or hepatic). Lymph nodes with a short axis diameter of <1.0 cm must increase by ≥50% and to a size of 1.5x1.5 cm or >1.5 cm in the long axis, 3) 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis. PD was defined as clinical PD, new non-nodal lesions or new nodal lesion ≥1.5 cm in GTD, progression of existing non-index lesions or bone marrow that was negative and now positive.
Measured: 6, 12, and 24 months
Kaplan-Meier Estimate of the Overall Survival (OS) in the DE Cohorts
OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.
Measured: From first dose of study medication through 2 year follow-up period
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the DE Cohorts
OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.
Measured: 6, 12, and 24 months
Kaplan-Meier Estimate of the OS in the MTD Confirmation/EE Cohorts
OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.
Measured: From first dose of study medication through 2 year follow-up period
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts
OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.
Measured: 6, 12, and 24 Months
Mean Inotuzumab Ozogamicin Serum Concentrations
Pharmacokinetic (PK) samples were required for participants enrolled in the confirmatory and preliminary efficacy MTD cohorts only (Parts 2 and 3). Concentrations of inotuzumab ozogamicin in serum were determined using appropriate, validated unconjugated (also known as free) bioanalytical assays.
Measured: Pre-dose on Cycle 1, Day 2; Pre-dose, 1 and 3 hours post-dose on Cycle 3, Day 2; 24 hours post-dose on Cycle 3, Day 3 and 168 hours post-dose on Cycle 3, Day 8.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2010 (estimated)
- Study startMar 2010
- Primary completionJul 2013
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, B-CellStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- UCB Pharma
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01055496
- Sponsor's protocol ID
- 3129K2-1105
- Other IDs
- B1931003, 2009-015497-35, 2009
- Status last verified
- Jun 2019
- First submitted
- 21 Jan 2010
- Last updated
- 2 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Sangha R, Davies A, Dang NH, Ogura M, MacDonald DA, Ananthakrishnan R, Paccagnella ML, Vandendries E, Boni J, Goh YT. Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma. J Drug Assess. 2017 Aug 16;6(1):10-17. doi: 10.1080/21556660.2017.1315336. eCollection 2017.
PubMed 28959500Ogura M, Tobinai K, Hatake K, Davies A, Crump M, Ananthakrishnan R, Ishibashi T, Paccagnella ML, Boni J, Vandendries E, MacDonald D. Phase I Study of Inotuzumab Ozogamicin Combined with R-CVP for Relapsed/Refractory CD22+ B-cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2016 Oct 1;22(19):4807-4816. doi: 10.1158/1078-0432.CCR-15-2488. Epub 2016 May 6.
PubMed 27154915
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AN OPEN-LABEL, PHASE 1 STUDY OF R-CVP OR R-GDP IN COMBINATION WITH INOTUZUMAB OZOGAMICIN IN SUBJECTS WITH CD22-POSTIVE NON-HODGKIN'S LYMPHOMA
- ClinicalTrials.gov ID
- NCT01055496
- Acronym / sponsor ID
- 3129K2-1105
- Conditions
- Lymphoma, B-Cell
- Keywords
- Non-Hodgkin's lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- UCB Pharma
- Study start
- Mar 2010 (actual)
- Primary completion
- Jul 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 25 Jan 2010 (estimated)
- Results
- Posted 2 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1 trial designed to evaluate safety and tolerability of chemotherapy in combination with inotuzumab ozogamicin, an investigational product, in adults with CD22-positive non-Hodgkin's lymphoma. The trial will involve two arms. In one arm, subjects will receive chemotherapy regimen R-CVP (rituximab, cyclophosphamide, vincristine and prednisone). In the other arm, subjects will receive R-GDP (rituximab, gemcitabine, cisplatinum and dexamethasone). Subjects in both arms will also receive inotuzumab ozogamicin.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (R-CVP) | Experimental | Drug: inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisoneSubjects in arm 1 will be enrolled in dose escalation cohorts that will initially evaluate an escalating dose of cyclophosphamide in combination with set doses of inotuzumab ozogamicin, vincristine, prednisone, and rituximab. |
| Arm 2 (R-GDP) | Experimental | Drug: inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasoneSubjects in arm 2 will be enrolled in dose escalation cohorts that will initially evaluate escalating doses of gemcitabine and/or cisplatinum in combination with set doses of inotuzumab ozogamicin, dexamethasone, and rituximab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Dose escalation cohorts: subjects with diagnosis of CD22-positive Non-Hodgkin's Lymphoma (NHL) who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy.
- Expanded maximum tolerated dose (MTD) confirmation and preliminary efficacy cohorts: subjects with diagnosis of CD22-positive NHL who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy or newly diagnosed subjects who are not candidates for anthracycline-based therapy.
- At least 1 measurable disease lesion that is > 1 cm in the longest transverse diameter, with a product of the diameters > 2.25 cm2 by CT or magnetic resonance imaging (MRI).
Key exclusion criteria (4 listed)
- Candidate for potentially curative therapy such as stem cell transplantation.
- Prior allogeneic hematopoietic stem cell transplantation (HSCT).
- Prior autologous transplantation, radioimmunotherapy, or other anti CD22 immunotherapy <= 6 months before the first dose of investigational product.
- More than 3 previous combination chemotherapy (2 or more cytotoxics) anticancer regimens.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisoneAlso: CMC-544Day 1: Rituximab at 375 mg/m2 Cyclophosphamide at 375 mg/m2 (cohort 1), 550mg/m2 (cohort 2), 750 mg/m2 (cohort 3, 4) Vincristine at 1.4 mg/m2 (max 2 mg) Day 2 Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2, 3), 1.3 mg/m2 (cohort 4) Days 1-5: Prednisone at 40 mg/m2 Each cycle is 3 weeks, with a maximum of 6 cycles total. | Drug | Arm 1 (R-CVP) |
| inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasoneAlso: CMC-544Day 1: Rituximab at 375 mg/m2 Gemcitabine at 500 mg/m2 (cohort 1, 2b, 3b), 1000mg/m2 (cohort 2a, 3a, 4, 5) Cisplatin at 37.5 mg/m2 (cohort 1, 2a), 50mg/m2 (cohort 2b, 3a), 75mg/m2 (cohort 3b, 4, 5) Day 2: Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2a, 2b, 3a, 3b, 4), 1.3mg/m2 (cohort 5) Days 1-4: Dexamethasone at 40 mg Each cycle is 3 weeks, with a maximum of 6 cycles total. | Drug | Arm 2 (R-GDP) |
Primary outcome
Participants Reporting Dose Limiting Toxicity (DLT) Adverse Events (AEs) for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 1
Time frame: From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.
DLT was defined as: febrile neutropenia, Grade (Gr) 4 neutropenia ≥7 days, Gr 4 thrombocytopenia ≥7 days, Gr 3/4 thrombocytopenia associated with bleeding requiring a transfusion, Gr 3/4 non-hematologic toxicity (except alopecia) ≥7 days or treatment-related and clinically significant irrespective of duration, ≥Gr 3 QTc prolongation, Gr 4 alanine or aspartate aminotransferase, Gr 2 hyperbilirubinemia (greater than (>)1.5 x upper normal limit) >7 days, delayed recovery from a treatment-related toxicity that prevented re-dosing by >7 days, or Granulocyte-colony stimulating factor treatment during the first cycle.
Participants Reporting DLT AEs for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 2
Time frame: From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.
DLT was defined as: febrile neutropenia, Grade (Gr) 4 neutropenia ≥7 days, Gr 4 thrombocytopenia ≥7 days, Gr 3/4 thrombocytopenia associated with bleeding requiring a transfusion, Gr 3/4 non-hematologic toxicity (except alopecia) ≥7 days or treatment-related and clinically significant irrespective of duration, ≥Gr 3 QTc prolongation, Gr 4 alanine or aspartate aminotransferase, Gr 2 hyperbilirubinemia (greater than (>)1.5 x upper normal limit) >7 days, delayed recovery from a treatment-related toxicity that prevented re-dosing by >7 days, or Granulocyte-colony stimulating factor treatment during the first cycle.
Percentage of Participants With Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) According to International Response Criteria for NHLs in the MTD and EE Cohorts
Time frame: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks.
OR was evaluated according to the International Response Criteria for NHLs. CR was defined as complete disappearance of all lesions and disease-related symptoms; all nodes must have decreased to normal (less than or equal to [≤]1.5 centimeters [cm] in their greatest transverse diameter (GTD) for nodes >1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy. PR was defined as >50% decrease in the sum of the product diameters (SPD) of up to 6 index lesions. No increase in size of other nodes, liver or spleen. Splenic and hepatic nodules must have regressed by ≥50% in the SPD or GTD (for single nodules). With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.
Percentage of Participants With a Treatment Emergent AE
Time frame: SAEs were assessed from informed consent through and including the end of treatment visit (at least 28 calendar days after last study drug administration). Non-SAEs were recorded from time of the first dose of study drug through last participant visit.
An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event may not necessarily have had a causal relationship with the treatment or usage. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were defined as those occurring on or after the first study drug dose day through and including 56 days post last dose of study drug. The severity of all AEs was graded by the investigator using the National Cancer Institute Common Terminology Criteria for AE Version 3.0 (NCI CTCAE v3.0).
Percentage of Participants With Any Grade 3/4 Chemistry Abnormality During Therapy
Time frame: Within 3 days prior to the start of each cycle, on Day 8 of each cycle, on Day 15 of Cycles 1, 2, and 3, and the end-of-treatment visit. Each Cycle is 21 Days.
The following parameters were analyzed for blood chemistry: blood urea nitrogen (or urea), creatinine, glucose, calcium, sodium, potassium, phosphorus, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, total bilirubin (and direct bilirubin, if total bilirubin was elevated), alkaline phosphatase, uric acid (or urate), albumin and total protein. Laboratory test results were graded using the NCI CTCAE v3.0 where CTCAE Grade 3 equals "severe" and CTCAE Grade 4 equals "life threatening or disabling."
Percentage of Participants With Any Grade 3/4 Hematology Abnormality During Therapy
Time frame: Within 3 days prior to the start of each cycle, Day 8 of each cycle, Day 15 of Cycles 1, 2, and 3, and the end-of-treatment visit. Each Cycle is 21 Days.
The following parameters were analyzed for hematology: lymphocytes, basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, monocytes, neutrophils, platelets, prothrombin international normalized ratio, prothrombin time, fibrinogen, and activated partial thromboplastin time. Laboratory test results were graded using the NCI CTCAE v3.0 where CTCAE Grade 3 equals "severe" and CTCAE Grade 4 equals "life threatening or disabling."
10 secondary outcomes
Percentage of Participants With a Best OR of CR or PR According to International Response Criteria for NHLs in the DE Cohorts
Time frame: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks.
Kaplan-Meier Estimate of the Progression-Free Survival (PFS) in the DE Cohorts
Time frame: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the DE Cohorts
Time frame: 6, 12 and 24 months
Kaplan-Meier Estimate of the PFS in the MTD Confirmation/EE Cohorts
Time frame: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts.
Time frame: 6, 12, and 24 months
Kaplan-Meier Estimate of the Overall Survival (OS) in the DE Cohorts
Time frame: From first dose of study medication through 2 year follow-up period
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the DE Cohorts
Time frame: 6, 12, and 24 months
Kaplan-Meier Estimate of the OS in the MTD Confirmation/EE Cohorts
Time frame: From first dose of study medication through 2 year follow-up period
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts
Time frame: 6, 12, and 24 Months
Mean Inotuzumab Ozogamicin Serum Concentrations
Time frame: Pre-dose on Cycle 1, Day 2; Pre-dose, 1 and 3 hours post-dose on Cycle 3, Day 2; 24 hours post-dose on Cycle 3, Day 3 and 168 hours post-dose on Cycle 3, Day 8.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28959500Sangha R, Davies A, Dang NH, Ogura M, MacDonald DA, Ananthakrishnan R, Paccagnella ML, Vandendries E, Boni J, Goh YT. Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma. J Drug Assess. 2017 Aug 16;6(1):10-17. doi: 10.1080/21556660.2017.1315336. eCollection 2017.
- Derived from this study: PubMed 27154915Ogura M, Tobinai K, Hatake K, Davies A, Crump M, Ananthakrishnan R, Ishibashi T, Paccagnella ML, Boni J, Vandendries E, MacDonald D. Phase I Study of Inotuzumab Ozogamicin Combined with R-CVP for Relapsed/Refractory CD22+ B-cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2016 Oct 1;22(19):4807-4816. doi: 10.1158/1078-0432.CCR-15-2488. Epub 2016 May 6.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
28 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone and inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone in people with Lymphoma, B-Cell, run by Pfizer at 28 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, United Kingdom, Canada, France, Japan and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants Reporting Dose Limiting Toxicity (DLT) Adverse Events (AEs) for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 1 (time frame: From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01055496, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2019.